Synthesis of monosubstituted β-cyclodextrin derivatives for medicinal applications Abstract This thesis is focused on preparation of a set of β-cyclodextrin derivatives with potential use as scaffolds for a construction of novel MRI contrast agents. Firstly, the skeleton of native β-CD was selectively persubstituted at possitions 6 and equipped with azide functions. Per-6-azido-β-CD was then monosubstituted on secondary face of the macrocycle. (E)-cinnamylbromide and propargylbromide were chosen as suitable reagents. The monosubstitution reaction afforded two types of regioisomers, substituted at position 2I -O- or 3I -O-. These regioisomers were sucessfully separated via preparative column chromatography after peracetylation of all free hydroxyl groups. 2I -O-, 3I -O-formylmethyl- and 3I -O- karboxymethyl- analogues were prepared by oxidative transformation of cinnamyl group. Finally the usability of the formylmethyl- derivative for covalent binding with suitable substrate via reductive amination was confirmed. Keywords: cyclodextrins, monosubstitution, cinnamyl, propargyl, formylmethyl, carboxymethyl, reductive amination, MRI, contrast agents

ABSTRACT This work is focused on the synthesis of a family of new macrocyclic ligands with exchangeable protons on coordinating groups that could potentially serve (after complexation with suitable paramagnetic lanthanide(III) ions) as responsive contrast agents (CAs) for magnetic resonance imaging (MRI). It is expected that measurement of extracellular pH should bring information for tumorous disease diagnoses and/or for suggesting the most efficient treatment. Therefore, our attention was focused on pH-dependent CAs based on a PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) mechanism capable of reporting pH changes in tissue. The PARACEST-related properties of a series of Ln(III) complexes with the CEST effect caused by amino groups coordinated to the central Ln(III) metal ions were investigated. Such a kind of PARACEST CA is new and has had no precedent in the literature. It was shown that these Ln(III) complexes produce a pH-sensitive PARACEST effect in the pH region relevant for living systems. The study brings proof-of-principle for utilization of complexes with a linear diamine pendant arm, i.e. complexes with two exchanging proton pools, for ratiometric pH determination by MRI independently on the probe concentration. In addition, to ensure a higher kinetic inertness of the...

Elektronová spinová rezonance (ESR) je neinvazivní spektroskopická technika založená na magnetické rezonanci. Používá se v mnoha vědních oborech jako biologie, chemie a fyzika pro zkoumání systémů s nepárovými elektrony. Tato dizertační práce se věnuje spektroskopii vysokofrekvenční rezonance spinů elektronů (HF-ESR) a jejímu použití na paramagnetické koordinační sloučeniny. V první části je představen teoretický základ s rešerší literatury v této oblasti a jsou představeny aplikace HF-ESR. Dále jsou představeny metody použité ke studování těchto systémů. Zde jsou popsány doplňující metody (XPS, RS, UV-VIS, AFM, SEM) pro zkoumání vzorků a je představen návrh nové sublimační komory vysokého vakua, která byla sestavena pro tvorbu tenkých vrstech koordinačních sloučenin na površích. Následují výsledky dosažené pomocí HF-ESR na molekulárních kvantových bitech [Cu(dbm)2], jednomolekulárních magnetech [CoX2(dppf)], [Co(4MeO-L)2Cl2] a je nastíněna vize bolometrů na bázi grafenu pro detekci této třídy sloučenin. Výsledky jsou diskutovány a jejich implikace jsou shrnuty v závěru. Reference a autorské výstupy pak uzavírají celou tuto práci.

Inflammatory bowel disease is a serious condition with an incomplete etiology and pathogenesis. In this thesis, a mouse model of sodium dextran sulfate-induced inflammation was used to study different changes in the metabolism of germ-free and conventionally raised mice due to the development of the inflammatory process. NMR metabolomics of fecal, urine and serum samples, combined with uni- and multivariate statistical analysis, were used to characterize the changes. It was shown that the metabolic signature differs between germ-free and conventional mice. In germ-free mice, significant amounts of carbohydrates were found in feces. Their levels decreased during inflammation as they were excreted in urine. In contrast to conventional mice, germ-free mice also excreted large amounts of amino acids in feces during the developing inflammation. Disorders of sugar and protein metabolism found in germ-free mice indicate severe malnutrition caused by inflammation. The results show that the presence of a microbiome represents a protective mechanism against significant disruption in the body. A stability study of fecal extracts of healthy conventionally colonized mice confirmed that none of the identified and quantified metabolites showed significant systemic changes in several consecutively collected...

of the thesis Considerable research attention has been paid to the neural regulation of the lower urinary tract (LUT) in past three decades. The aim of this work is mapping of a brain activity by functional magnetic resonance imaging (fMRI) using refined scanning protocol with synchronously performed urodynamics. We aimed to detect neural activity associated with pelvic floor muscle (PF) contractions, filling of urinary bladder and miction. In addition we evaluated using fMRI brain activity associated with urinary bladder filling in patients with a complete spinal cord injury (SCI). We hypothesized activation of brainstem and forebrain areas in receiving information from the vagal nerves. Adjustments of urodynamic system enabled successful implementation of synchronous filling cystometry with fMRI evaluation of cortical activity. We concluded that synchronous urodynamic examination is a novel feasible method that facilitates and enhance interpretation of fMRI data acquired. The main clusters of brain activation during PF contractions were observed in the medial surface of the frontal lobe (primary motor area) and supplementary motor area (SMA). We detected neural activity associated with filling of urinary bladder and miction in middle and inferior frontal gyrus, angular gyrus, posterior and...

This thesis deals with switched mode power supplies based on resonant principle to achieve high efficiency. Several ways of switched mode power supplies optimalisation are described as part of the work to achieve better efficiency. Priparily, the new generation of switching elements based on SiC and resonant topology are used to achieve significant switching loss minimization. The selected resonant topology is simualted in detail and then built with focus on high efficiency. The main content of the work consists in the design and realization of the switched mode power supply with selected control algorithms and their comparison. The problems associated with usage of new SiC MOSFET generation in TO-247-4L package are being solved within the design and implementation of the power source. To solve the main problems, new 3rd SiC MOSFET gate driver was developer for working with switching frequencies in hundreds of kHz and resisting very high voltage stress on the controlled transistor. The next part of the gate driver is the overcurrent protection. The overcurrent limit can be set easily by changing one component. This protection reacts very quickly in hundreds of nanoseconds, so it is capable of saving the converter even in branch failure and going to hard short circuit. The functional sample of the series resonant converter was built and revated in the work. The converter based on 3. Generation of SiC MOSFET transistors from Cree in a modern case TO-247-4L was built. For this inverter, it was also necessary to develop both the control scheme and the resonance frequency tracking to achieve accurate switching and thus achieve the use of the resonant principle of the converter to the maximum extent possible. The result of this work is up to 3 kW converter with adjustable output voltage while maintaining high efficiency up to 96%.

The diploma work is dealing with an influence of postural muscles on preschool children singing expression as weel as on connection between a posture and a breathe. The aim of this diploma work is not just a clarification of this issue, but primaliry it is an aspiration of creating a methodology of exercises, which leads to an improvement of children`s singing. Experimental part of this diploma work is concerned with a verification of created methodology on constant group of preschool children. An audio CD with records of children singing expressions, which confirms reached verdicts, is included.

Perfusion magnetic resonance imaging is modern diagnostic method used mainly in oncology. In this method, contrast agent is injected to the subject and then is continuously monitored the progress of its concentration in the affected area in time. Correct determination of the arterial input function (AIF) is very important for perfusion analysis. One possibility is to model AIF by multichannel blind deconvolution but the estimated AIF is necessary to be scaled. This master´s thesis is focused on description of scaling methods and their influence on perfussion parameters in dependence on used model of AIF in different tissues.

Tato disertační práce analyzuje artefakty v NMR obrazech. V lékařské praxi mohou artefakty zabránit diagnostice patologických tkání, a proto je třeba tyto nežádoucí jevy odstranit. Vzhledem k nutnosti vyloučit artefakty způsobené nehomogenitou statického magnetického pole jsou v dané souvislosti diskutovány také nové možnosti měření deformací. Práce popisuje metodu pro měření základního pole i RF pole a jejich nehomogenit na základě měření MR obrazů T2 a T2*. Metoda kombinuje akviziční postupy pro spinové a gradientní echo za účelem rozlišení relaxačních časů T2 a T2*. V této souvislosti také vyvstává potřeba provést exponenciální aproximaci relaxačního procesu. Experimentální výsledky pro plastové i měděné vzorky jsou prezentovány v příslušné části práce. Pokud jde o vlastní členení popisovaných jevů, je třeba uvést, že významný problém představují artefakty způsobené magnetickou susceptibilitou. Různé hodnoty magnetické vodivosti na rozhraní mezi dvěma materiály mohou způsobit deformaci magnetického pole, přičemž může dojít i k úplné ztrátě signálu.

<p>Akutni pankreatitis predstavlja zbirni pojam dinamičkih, lokalnih i sistemskih patofiziolo&scaron;kih procesa nastalih iznenadnim prodorom aktivnih litičkih pankreasnih enzima u žlezdani parenhim. Cilj istraživanja je da se Utvrditi senzitivnost difuzione sekvence magnetne rezonance (DWI) radi utvrđivanja morfolo&scaron;kih promena parenhima kod akutnog pankreatitisa. Poređenje difuzione mape i difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kod pacijenata sa morfolo&scaron;ki urednim parenhimom pankreasa na magnetnoj rezonanci. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na pol. Utvrditi da li postoje statistički značajne razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom u odnosu na godine. Odrediti prelomnu tačku difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom. Studija je bila prospektivnog karaktera i obuhvatilo je 30 ispitanika sa morfolo&scaron;ki urednim parenhimom pankreasa i 30 sa dijagnozom akutnog pankreatitisa unutar 72 sata od početka simptoma. Svi pacijenti su pregledani magnetnom rezonancom u Centru za radiologiju, Kliničkog Centra Vojvodine. Rezultati ukazuju da postoje razlike difuzionog koeficijenta kod pacijenata sa akutnim pankreatitisom i kontrolne grupe. Takođe smo dokazali da difuzioni koeficijent zavisi od pola i starosti i utvrdili smo prelomnu tačku difuzije za rano dijagnostikovanje akutnog pankreatitisa.</p> / <p>Acute pancreatitis is defined as cumulative term of dynamic local and general pathophysiological processes caused by sudden penetration of active lithic pancreatic enzymes in the glandular parenchyma. Goal of this research is to note the changes (sensitivity) in values of diffusion weighted images (DWI) in acute pancreatitis and to determine morphological changes in glandular parenchyma of pancreas. Comparation of DWI between patients with acute pancreatitis and patients with normal pancreatic parenchyma based on magnetic resonance (MRI). We also want to determine whether there were statistically significant differences of DWI in patients with acute pancreatitis in relation to sex and age. One of our goals also was to determine breakpoint of DWI as a sure sign of acute pancreatitis. This was prospective study and included 30 patients with morphologically healthy parenchyma of the pancreas (control group) and 30 with the diagnosis of acute pancreatitis &ndash; in first 72 hours of the onset of symptoms. All patients were examined on MRI in department of Radiology of Clinical Center of Vojvodina. Our results indicate that was a big difference of DWI between patients with acute pancreatitis and control group. We prove that DWI depends on the sex and age. 1,77x10-6mm/s2 was breakpoint which indicates acute pancreatitis.</p>